# Pathophysiological impact of subtypes of eosinophil cell death

> **NIH NIH F31** · UNIVERSITY OF CINCINNATI · 2024 · $46,386

## Abstract

Project Summary
Eosinophils (eos) are a subset of white blood cells that are involved in multiple immune diseases, broadly termed
eosinophilic-associated diseases (EAD). Whether they are protective or contribute to disease pathology is not
always clear. For instance, eos are central to fighting infections caused by parasites. However, in asthma they
have been shown to cause tissue damage, as well as participate in tissue repair and regeneration. Our lab has
recently focused on eosinophilic heart disease, a serious consequence of hypereosinophilia in patients. The
function of eos in physiology and pathology is often correlated with the extracellular presence of their cytoplasmic
contents. Indeed, in the mouse model of eosinophilic heart disease that we developed, we see the presence of
extracellular eosinophil granules intimately associated with dying cardiomyocytes. Eos cytoplasmic contents are
released through a process of degranulation. Various methods of degranulation including cytolysis, a non-
apoptotic cell death, have been characterized. Although cell death is a natural and essential process in the life
cycle of all cells and organisms, the mechanism of cell death has significant impact on tissue homeostasis,
immune response, and diseases. This is particularly true for terminally differentiated cells like eos, whose
accumulation at sites of disease is regulated by recruitment and survival versus cell death stimuli. There are
several mechanisms of cell death, including apoptosis, accidental/non-regulated necrosis, and regulated
necrosis. The latter is a spectrum of cell death types that are different from the classical type of necrosis in that
they are triggered by specific stimuli and mediated by specific signaling pathways. Importantly, this makes it a
targetable process. Currently these cell death mechanisms have not been well characterized in eos. In my
preliminary studies, I have generated in vitro models of multiple eosinophil cell death types, using diverse stimuli
(staurosporine, ligation of Fas receptor, TNF𝛼 in presence of apoptosis inhibitor, H2O2, calcium ionophore) and
measuring different outcomes (expression of annexin V on outer plasma membrane leaflet, permeability to
7AAD, active caspase-3), which will be used to characterize mechanisms of eosinophil cell death.
Understanding mechanisms of eosinophil cell death that are destructive to tissue could provide novel targeted
therapies for EAD. Our long-term goal is to develop novel rational therapies for EADs based on understanding
of mechanisms of disease. The overall goal of this proposal is to define and characterize the different eos cell
death mechanisms and their impact on disease pathogenesis.

## Key facts

- **NIH application ID:** 10825101
- **Project number:** 1F31HL172649-01
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Immaculeta Kasarachi Osuji
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,386
- **Award type:** 1
- **Project period:** 2024-09-16 → 2026-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825101

## Citation

> US National Institutes of Health, RePORTER application 10825101, Pathophysiological impact of subtypes of eosinophil cell death (1F31HL172649-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10825101. Licensed CC0.

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